BACKGROUND AND PURPOSE: Evolution of minimally invasive techniques has prompted interest in natural orifice transluminal endoscopic surgery (NOTES). Challenges for NOTES include loss of instrument rigidity, reduction in working envelopes, and collision of instrumentation. Magnetic anchoring and guidance system (MAGS) is one surgical innovation developed at our institution whereby instruments that are deployed intra-abdominally are maneuvered by the use of an external magnet. We present our initial animal experience with complete transvaginal NOTES nephrectomy using MAGS technology. MATERIALS AND METHODS: Transvaginal NOTES nephrectomy was performed in two female pigs through a vaginotomy, using a 40-cm dual-lumen rigid access port inserted into the peritoneal cavity. A MAGS camera and cauterizer were deployed through the port and manipulated across the peritoneal surface by way of magnetic coupling via an external magnet. A prototype 70-cm articulating laparoscopic grasper introduced through the vaginal access port facilitated dissection after deployment of the MAGS instruments. The renal artery and vein were stapled en-bloc using an extra-long articulating endovascular stapler. RESULTS: NOTES nephrectomies were successfully completed in both pigs without complications using MAGS instrumentation. The MAGS camera provided a conventional umbilical perspective of the kidney; the cauterizer, transvaginal grasper, and stapler preserved triangulation while avoiding instrument collisions. Operative duration for the two cases was 155 and 125 minutes, and blood loss was minimal. CONCLUSIONS: NOTES nephrectomy using MAGS instrumentation is feasible. We believe this approach improves shortcomings of previously reported NOTES nephrectomies in that triangulation, instrument fidelity, and visualization are preserved while hilar ligation is performed using a conventional stapler without need for additional transabdominal trocars.